MMP7基因多态性和吸烟交互影响与胃癌发生风险之间的关系

Relationship of gastric cancer and the interaction between MMP7 genetic polymorphism and tobacco smoking

[目的]本研究通过对基质金属蛋白酶7(matrix metalloproteinase 7,MMP7)启动子-181A[G](rs11568818)位点多态性的研究,探索其对MMP7启动子活性以及基因表达的影响,进一步阐明-181A[G]单核苷酸多态性与胃癌患病风险的关系。[方法]在2014年1月～2016年12月于我院就诊的患者中,选取120例符合条件的患者纳入本研究。其中包含无癌症的健康患者60例(对照组),以及确诊为胃癌的60例患者(胃癌组)。吸烟史2年以上的纳入研究组病例被定义为吸烟成瘾者。通过生理学、组织学、PCR以及Meta分析对病例病情以及MMP7基因多样性进行统计和分析。[结果]MMP7基因多态性分析表明,-181A[G]位点GG基因型比AA基因型与胃癌发病风险相关性更强(P=0.018,OR=1.93,95%CI=1.13～3.29)。烟草成瘾会增加GG基因型患者胃癌患病风险(P=0.03,OR=2.46,95%CI=1.07～5.68)。Meta分析显示,烟草中尼古丁可以显著增加AG和GG基因型病例MMP7的活性和表达,增加患胃癌发生风险。由尼古丁诱导的pCREB与基因MMP7的G等位基因启动子的优先结合,增强了基因的转录加强胃癌发病风险。[结论]MMP7基因启动子的-181A[G]位点G等位基因可增强胃癌发病风险。显示出尼古丁对MMP7的GG基因型在胃癌患病风险上的加成效应。

[Objective] The purpose of this research is to study the-181 A[G](rs11568818)polymorphism of matrix metalloproteinase 7(MMP7),exploring the effects of-181 A[G] polymorphism on the activity of MMP7 promoter and gene expression,explaining the relationship between the-181 A[G] polymorphism and risk of gastric cancer.[Methods]120 cases,which were treated and tested in our hospital from Jan.2014 to Dec.2016,were included in our study.Among them,there were 60 healthy cases with no cancer(control group),while 60 cases were diagnosed as gastric cancer(gastric cancer group).Patients with more than 2-year addictive smoking history were defined as tobacco addiction.Physiological and histological endpoints were used to define and classify states of illness,while PCR and Meta analysis were used to analyze the polymorphism of gene,and the relation to gastric cancer risk.[Results]The gene polymorphism analysis showed that GG phenotype of-181 A[G] in MMP7 gene had stronger correlation with gastric cancer risk than AA phenotype(P=0.018,OR=1.93,95%CI=1.13-3.29).Tobacco addiction could increase the risk of gastric cancer in patients with GG phenotype(P=0.03,OR=2.46,95%CI=1.07-5.68).Meta analysis indicated that tobacco nicotine significantly prompted the activity and expression of MMP7 in AG and GG genotype patients,and increased the risk of having gastric cancer.[Conclusion]The G allele on-181 A[G] of gene MMP7 promoter increased the risk of having gastric cancer.Combined with nicotine,GG genotype of MMP7 strongly increased the incidence of gastric cancer.